The field of the invention relates to systems and methods for providing stimulation of central nervous system tissue, muscles, or nerves, or combinations thereof. More particularly, the invention relates to providing neurostimulation to the vagus nerve and/or its branches to provide therapeutic outcomes, such as the treatment of pain, with signals that are adjusted based on pulmonary activity.
The electrical stimulation of a biological tissue, e.g., a muscle or a nerve, often afferent nerves, to indirectly affect the stability or performance of a physiological system can provide functional and/or therapeutic outcomes, and has been used for activating target muscles or nerves to provide relief for a variety of disorders. Many systems use stimulators (i.e., pulse generators) and electrodes to deliver electrical charge to the target site of the muscle or nerve. For example, electrical stimulation of the vagus nerve (VNS) is a validated, United States Food and Drug Administration approved therapy that has improved the lives of many individuals with epilepsy or depression. For example, VNS has been reported to have improved effects on sleep in epileptic patients, and immunomodulatory effects in depression patients.
VNS has also been used for a multitude of other conditions including overeating and Alzheimer's disease. Recent evidence suggests that VNS may have anti-nociceptive effects, particularly in patients with depression. Animal studies have linked stimulation of vagal afferents with antinociception. Both animal studies and recent human studies, suggest that during active VNS, pro-nociception can occur when stimulus intensity is low (e.g., about 30-60% of pain threshold, or approximately 0.5-2 mA or more or less), but anti-nociceptive effects predominate when stimulus intensity is high (e.g., just below or above pain threshold, or approximately greater than 2.5 mA or more or less). Moreover, chronic VNS (e.g., at mean values of about 0.7 to 1.4 mA) may raise pain thresholds (i.e., analgesia) for both tonic pinch and heat pain, as well mitigating the so-called pain wind-up phenomenon (a phenomenon related to central sensitization) when mechanical stimuli are applied. These results have been promising in terms of analgesia. Moreover, VNS has the advantage of greater side effects tolerance and better patient adherence because the VNS therapy is computer programmed, as compared to pharmacotherapy that requires patient adherence to a drug, e.g., pill regimen.
Unfortunately, classical VNS can also induce morbidity stemming either from co-activation of efferent vagal fibers (e.g., bradycardia, asystole, larynx/pharynx disorders, dysphagia), or from infection or hardware failure due to the invasive nature of VNS systems. VNS systems typically require open surgery to implant one or more electrodes on or near the vagal nerve, and may also include tunneling a lead to connect the electrodes to a pulse generator also implanted under the skin. The application of a less invasive vagus nerve stimulation therapy would allow VNS benefits to reach a larger percentage of afflicted populations.
Therefore, it would be an advance in the art to provide improved systems and methods for delivering electrical stimulation to the vagus nerve and/or its branches.